Fig. 2

Inhibition of iron mediated α-synuclein (α-syn) aggregation. Recombinant α-synuclein (186.6 μM) was incubated alone or in the presence of equimolar concentrations of iron nitrate (iron = Fe (NO₃)₃), PBT434 or PBT434-met. Thioflavin T (ThT) fluorescence was measured (RFU = relative fluorescent units) every 30 min for 42 h. The lag-time of aggregation was slowed by PBT434 (α-synuclein = 37 h, α-syn + iron = 10.2 h, α-syn + iron + PBT434 = 16.60 h and α-syn + iron + PBT434-met =7.9 h). a One Way ANOVA with games-howell post hoc analysis (unequal variances on the lag-phases, individual reaction wells (n = 5–6) showed that, α-syn + iron had significantly faster aggregation than α-syn + iron + PBT434 (p = 0.02) or α-syn alone (p = 0.04) but not α-syn + iron + PBT434-met (p = 0.49). Lower panels: Electron micrographs of samples from each reaction mixture were taken after 42 h (b; α- synuclein, no iron); c Increased fibril formation in the presence of iron; d Diminished fibril formation in the presence of PBT434; E) PBT434-met did not reduce the fibril formation